Plasma gas mixture for sterilizer and method

ABSTRACT

A method for plasma sterilization comprises exposing an article to be sterilized to a neutral active species of a plasma generated from a premixed gas mixture comprising oxygen, hydrogen, and a noble gas. The exposure of the article to the plasma is carried out at reduced pressures and a chamber temperature of less than 63° C. for a time period sufficient to effect sterilization. The apparatus for plasma sterilization of articles comprises a plasma generator, a sterilizing chamber, and a source of pressurized gas mixture in fluid communication with the plasma generator. The source of pressurized gas mixture has a noble gas and a substantially nonflammable mixture of hydrogen and oxygen, which is preferably between about 2.0 to 2.4 (v/v) percent hydrogen and between 2.6 to 3.0 (v/v) percent oxygen.

This application is a continuation-in-part of copending application Ser.No. 08/073,653, filed Jun. 7, 1993, now U.S. Pat. No. 5,413,759, whichis a continuation of application Ser. No. 07/817,714, filed Jan. 7,1992, now abandoned, which is a divisional of application Ser. No.07/576,292, filed Aug. 31, 1990, now U.S. Pat. No. 5,115,166, which is acontinuation-in-part of application Ser. No. 07/475,602, filed Feb. 6,1990, now abandoned, which is a continuation-in-part of application Ser.No. 07/321,483, filed Mar. 8, 1989, now abandoned.

FIELD OF THE INVENTION

This invention relates to sterilization of articles with gaseousspecies. In particular this invention relates to an apparatus and methodfor sterilizing articles with a neutral active species of a gas plasmagenerated from a gas mixture of oxygen and hydrogen in a noble gas suchas argon.

BACKGROUND OF THE INVENTION

Various gas sterilization methods have been investigated in the past.Methods using ethylene oxide and other disinfecting gases are widelyused for sterilizing a wide range of medical products frompharmaceutical preparations to surgical instruments. Irradiation aloneor together with disinfecting gases has also been investigated, assummarized by Russell, A., The Destruction of Bacterial Spores, NewYork: Academic Press (1982).

A sterilizing method must effectively render all microbial organismsnon-viable without damage to the article or goods being sterilized andits packaging. However, many disinfecting gases which meet thiscriteria, such as ethylene oxide and irradiation methods, have beenrecognized to expose workers and the environment to safety hazards.Recent legislation has been severely restricting the amount of hazardousgases such as ethylene oxide (a suspected carcinogen) in the workingenvironment, or the use of any system or method which produces toxicresidues or exhaust products. This has been presenting a major crisis inhospitals and other areas of the health industry.

DESCRIPTION OF THE PRIOR ART

The use of plasma to sterilize containers was suggested in U.S. Pat. No.3,383,163. Plasma is an ionized body of gas which may be generated bythe application of power from different sources. The ionized gas willcontact microorganisms on the surfaces of the items to be sterilized andeffectively destroy the microorganisms.

Sterilizing plasmas have been generated with a wide variety of gases:argon, helium, or xenon (U.S. Pat. No. 3,851,436); argon, nitrogen,oxygen, helium, or xenon (U.S. Pat. No. 3,948,601); glutaraldehyde (U.S.Pat. No. 4,207,286); oxygen (U.S. Pat. No. 4,321,232); oxygen, nitrogen,helium, argon, or freon with pulsed pressure (U.S. Pat. No. 4,348,357);hydrogen peroxide (U.S. Pat. No. 4,643,876); nitrous oxide, alone ormixed with oxygen, helium, or argon (Japanese Application Disclosure No.103460-1983); and nitrous oxide, alone or mixed with ozone (JapaneseApplication No. 162276-1983). Unfortunately, these plasmas have provento be too corrosive to articles being sterilized, and particularpackaging materials, have left toxic residues on the sterilizedarticles, or have presented safety or environmental hazards.

Non-plasma gas sterilization procedures have been described using ozone(U.S. Pat. No. 3,704,096) and hydrogen peroxide (U.S. Pat. Nos.4,169,123, 4,169,124, 4,230,663, 4,366,125, 4,289,728, 4,437,567, and4,643,876). These materials have certain process actions which limittheir sterilization applications and in some applications are toxic andleave undesirable residues.

Plasma gas sterilizer systems described in U.S. Pat. Nos. 3,851,436 and3,948,601 comprise a plasma RF generation chamber. A gas plasma producedin the chamber with argon, helium, nitrogen, oxygen, or xenon is passedinto a separate sterilization vacuum chamber. U.S. Pat. No. 4,643,876describes a hydrogen peroxide plasma RF generation chamber which alsofunctions as the sterilizing chamber. Matching networks are requiredwith the RF systems to adjust to the conductivity variations in theplasma generating zone.

SUMMARY OF THE INVENTION

A method aspect of this invention for plasma sterilization comprisesexposing an article to be sterilized to the neutral active species of aplasma generated from a gaseous mixture containing from 1 to 10 (v/v)percent oxygen and from 2 to 8 (v/v) percent hydrogen in a noble gas,and optimally being a gas mixture containing about 2.6 to about 3.0(v/v) percent oxygen, about 2.0 to about 2.4 (v/v) percent hydrogen, andthe rest being argon or helium delivered premixed from a pressurizedsource. The plasma induced gas sterilization is carried out at atemperature of 63° C. or less and a pressure of from 0.1 to 150 Torr,preferably 1 to 40 Torr.

An apparatus aspect of this invention for plasma sterilization ofarticles comprises a plasma generator and a sterilizing chamber. Theplasma generator has an inlet for receiving a premixed gas mixture froma pressurized source. The source of pressurized gas mixture is a singlecontainer (or multiple containers with the same contents) having a noblegas and further having a non-flammable mixture of hydrogen and oxygen.The gas mixture is preferably pressurized to between 2200 psig to about2500 psig, with the non-flammable mixture preferably being between about2.0 to 2.4 (v/v) percent hydrogen and between about 2.6 to 3.0 (v/v)percent oxygen.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a top view of a plasma sterilizer of this invention.

FIG. 2 is a front view of the plasma sterilizer embodiment of FIG. 1.

FIG. 3 is a cross-sectional view of the plasma sterilizer embodiment ofFIG. 1 and FIG. 2, taken along the line 3--3 in FIG. 2.

FIG. 4 is a cross-sectional view of the plasma sterilizer embodiment ofFIG. 3, taken along the line 4--4.

FIG. 5 is a cross-sectional view of tube 54 taken along line 5--5 inFIG. 3.

FIG. 6 is a cross-sectional view of tube 58 taken along line 6--6 inFIG. 3.

FIG. 7 is a cross-sectional view of tube 56 taken along line 7--7 inFIG. 3.

FIG. 8 is a partial cross-sectional view of the plasma generator tubeand assembly of the embodiment of FIG. 1.

FIG. 9 is a partial, fragmentary, cross-sectional detail view of theplasma generator tube of the plasma generator shown in FIG. 8.

FIG. 10 is a cross-sectional view of the waveguide of the embodiment ofFIG. 1, taken along the line 10--10 in FIG. 3.

FIG. 11 is a side cross-sectional view of an alternate single waveguideembodiment of the plasma sterilizer of this invention.

FIG. 12 is a cross-sectional view of the waveguide of the embodiment ofFIG. 11, taken along the line 12--12.

FIG. 13 is a side cross-sectional view of a multiple magnetronembodiment of this invention.

FIG. 14 is a front cross-sectional view of the multiple waveguideembodiment of the plasma sterilizer of this invention, taken along theline 14--14 of FIG. 13.

FIG. 15 is a partial cross-sectional view of the plasma generator tubeand assembly of the embodiment of FIG. 13.

FIG. 16 graphically illustrates a typical survivor curve when practicingthe invention using a plasma generated from a gas mixture according tothe invention. A biological indicator (here Bacillus circulans) was usedwith the vertical axis being a logarithmic scale of survivors and thehorizontal axis being time in minutes.

DETAILED DESCRIPTION OF THE INVENTION

Hospitals originally relied on disinfectants and steam autoclaves forsterilizing implements. In more recent years, ethylene oxide gassterilization has made possible the sterilization of packaged articles,drugs, and medical supplies, and hospital systems are highly dependentupon these procedures. However, ethylene oxide is now suspected to be adangerous carcinogen and a number of new state laws protecting workersafety and the environment are restricting further use of ethylene oxidesterilizers in hospital environments. In addition, ethylene oxide isknown to be a dangerous material from several other aspects. In its pureform it is explosive and flammable and therefore requires that allequipment must be so designed as to be classified as non-explosive. Themost popular form of the diluted or non-explosive mixtures containsfluorocarbons (Freon), which are no longer environmentally acceptable.Also, because it is a highly suspected carcinogen, which has resulted instringent regulations by State and Federal authorities regardingprotection of worker safety and emissions to the environment, furtherburdens and restrictions have been placed on the use of ethylene oxidesterilizers in all applications.

Numerous gas plasma sterilizers using a wide variety of gases have beendescribed in the patent literature. A few have been commerciallyproduced. A few have focused on residue contamination problems. Thepreviously described gas sterilizers fail to satisfy current regulatoryresidue and exhaust emission safety standards of several states becausethey leave unacceptable residues, produce exhaust emissions which arepotentially hazardous to hospital personal, or cause unacceptabledestruction of packaging materials. By substituting one hazard foranother, they are thus not satisfactory for replacing ethylene oxidesterilizers.

The gas sterilizer of this invention produces a plasma from a gasmixture containing a noble gas, such as argon or helium, together with anonflammable mixture of oxygen and hydrogen. This mixture can bedesignated as non-flammable due to the concentration of flammable orcombustion supportive gases being below defined levels of flammability,as evidenced in industry accepted standards published by the Bureau ofMines. Reference Bureau of Mines Bulletin 503, "Limits of Flammabilityof Gases and Vapors" and Bulletin 627, "Flammability Characteristics ofCombustible Gases and Vapors". According to Lewis et al., CombustionFlame and Explosions of Gases, Academic Press (1951), the lower limit offlammability of hydrogen in air is 4.00% (v/v).

The exhaust gas products of the gas mixture after use in thesterilization process fully satisfy current environmental and workersafety concerns, as the products of the plasma are almost entirely watervapor, carbon dioxide and non-toxic gases normally found in theatmosphere.

The plasma is produced as a result of an applied electric orelectromagnetic field, including any accompanying radiation which mightbe produced. The electromagnetic field can cover a broad frequencyrange, and can be produced by a magnetron, klystron, or RF coil. Forpurposes of clarity of presentation and not by way of limitation, thedescription hereinafter describes the use of a magnetron as theelectromagnetic field source, and the use of all other suitable sourcesof the electromagnetic field required for plasma production are intendedto be included in this invention, including without limitation,magnetrons, klystron tubes, RF coils, and the like.

The term "sterilization" connotes a process by which all viable forms ofmicroorganisms are destroyed or removed from an object. Sincemicroorganisms die according to first order chemical kinetics, it iscustomary to define sterility in terms of "probability of survivors."The practical goal of a sterilization process is therefore measured as aprobability (e.g., 10⁻³, 10⁻⁶, 10⁻¹²), the probability indicating thelethal effect of a particular sterilizing dose or regimen. It is usualto assume increased time of exposure to a set of sterilizing conditionswill decrease the probability of survivors accordingly. Doubling thesterilizing time of identical conditions would result in a doubling ofthe exponent of the probability term, for example 10⁻⁶ would become10⁻¹².

Broadly, the present invention can be viewed as essentially requiring aplasma generator, a sterilizing chamber, and a source of pressurized gasmixture in fluid communication with the plasma generator. Although aparticularly preferred apparatus will be described with certain plasmagenerator and sterilizing chamber component embodiments, and withreference to a method for plasma sterilization comprising exposing anarticle to be sterilized to a neutral active species of a plasmagenerated from a particular gas mixture, it should be understood thatvariations in the preferred apparatus component and in the method arewithin the scope of this invention. For example, U.S. Pat. No.5,244,629, issued Sep. 14, 1993, the disclosure of which is incorporatedby reference, describes a pulsed treatment with one or morepulsed-vacuum cycles but where one cycle involves exposing the articleto be sterilized to a neutral active species of a gas plasma. This gasplasma may be generated from the inventive gas mixture as is hereinafterfurther described and exemplified.

Turning to FIG. 1, a top view is illustrated with FIG. 2 illustrating afront view of a single waveguide plasma sterilizer embodiment of thisinvention. The plasma sterilizer has a plasma generator 2 and asterilizing chamber 4. The plasma generator 2 comprises anelectromagnetic field generator such as a magnetron 6 and a waveguide 8which directs the electromagnetic field. The plasma source gases aredirected into plasma generating and delivering tubes 10, 12, and 14 byfeeder tubes from gas delivery tubes 16, 18, and 20 leading from thecontrol valve complex 22.

Individual gases are fed from one, or a plurality of pressured gascanisters, in which substantially the same, premixed gas composition iscontained. Typical initial pressures are in the range of about 2200 toabout 2500 psig. The cylinder is replaced when the pressure drops toabout 50 to 100 psig (about 350-700 kPa).

For example, the premixed gas mixture can be stored under pressure in astandard gas cylinder equipped with a valve and a connecting fitting asspecified by the Compressed Gas Association. The cylinder pressure canbe reduced and regulated by using a standard, conventional gasregulator, which may be mounted to the gas cylinder by a mating CGAfitting. The gas will then flow during practice of the sterilizingmethod at the desired rate from the regulator to the sterilizer throughconventional tubing connected with conventional gas tight fittings.

The preferred gas concentrations of the premixed gases in the gasmixture avoid the potential problem of flammability otherwise possiblewith an oxygen/hydrogen gas mixture in a noble gas carrier.Nevertheless, although these preferred concentrations are relativelylow, the mixture is still useful as the source gas for a plasma formedspecies having sporicidal activity, as will be exemplified hereinafter.

The optimum gas mixture is about 2.2 ±0.2 (v/v) percent hydrogen, about2.8 ±0.2 (v/v) percent oxygen, and the balance argon or helium, withthis mixture being provided from a single container, such as a singlepressurized gas canister. Other noble gases could be used (neon, xenon,krypton), but they are less preferred due to expense. Unlike prior artsterilizers with a plurality of different pressurized gas sourcesdesigned to be fed through regulating and sensing components, thepresent invention represents a simpler apparatus since it eliminatessuch multiple regulating and sensing components required for feed linesfrom different gas cylinders. Consequently, overall operatingperformance and reliability are enhanced by eliminating the possibilityof incorrect mixture proportions that could result from componentfailures or operator error. Additionally, routine operating costs arereduced and maintenance simplified.

Such a premixed gas composition of the invention may be fed by inletlines 24, 25, and 26. The operation of the control valves in valvecomplex 22 is controlled by the central processing unit (CPU) 28 bystandard algorithms or logic code or operating software. The controlvalves and CPU can be any of the conventional, standard devices used forgas flow control in plasma generating equipment.

The sterilizing chamber 4 may comprise top plate 30, side plates 32 and34, bottom plate 36, back plate 37, and front sealing door 38 throughwhich articles or materials to be sterilized are placed in the chamber.The plates are shown attached together in a sealed relationship to forma vacuum chamber, such as by welding. The door 38 is secured in a sealedrelationship with the sterilizing chamber. It is attached to the chamberin a practical manner such as tracts or hinges at the top, side, orbottom with, in the case of apparatus shown, conventional hinge pins(structure not shown) to swing against abutting surfaces and an O-ringseal 40 (FIG. 3) of the side, top, and bottom plates, where the pressuredifference between the internal chamber vacuum pressure and thesurrounding atmospheric pressure holds it tightly in place. However, thedoor could also be constructed to slide open and to be closed.

The plates and door can be made of any material having the strengthrequired to withstand the external atmospheric pressure when the chamberis evacuated. Stainless steel or aluminum plates and door can be used.The internal surface material of the chamber is critical and greatlyaffects the number of killing species available in the chamber. Oneuseful material is pure (98%) aluminum which can be applied either as aliner or as a flame-sprayed coating on all internal walls of thestainless steel chamber. An alternate material is nickel. However, weprefer to coat the chamber interior with an inert polymer coating (e.g.Teflon).

The gases are exhausted from the sterilizing chamber through exhaustoutlet port 42 to a conventional vacuum pump system (not shown).

FIG. 3 is a top cross-sectional view of the plasma sterilizer embodimentof FIG. 1 and FIG. 2, taken along the line 3--3 in FIG. 2. FIG. 4 is aside cross-sectional view of the plasma sterilizer embodiment of FIG. 1and FIG. 3, taken along the line 4--4 in FIG. 3. Each of the plasmagenerators 10, 12, and 14 comprise an inlet cap 44 with a gas inlet port48 leading to a respective gas generator tube 51, 52, or 53 leadingthrough the waveguide 8. In the waveguide 8, the gases are energized andconvert in tubes 51, 52, and 53 to a plasma. The gas generator tubedirects the plasma flow into the gas distribution tubes 54, 56, and 58from which the plasma is fed into the sterilizing chamber 60. The gasgenerator tubes are enclosed in tubular metal cooling tubes 62 and 64.The caps 44 and the cooling tubes 62 and 64 are preferably provided withgroves or cooling fins (not shown) in a conventional manner to increasetheir efficiency in removing heat from gas generator tubes. The distalends of the gas distribution tubes 54, 56, and 58 are supported byspring-biased end supports 66 mounted on sideplate 32, but could bemodified for gas distributor plenum designs, as known in the art.

The door 38 is held in sealing engagement by atmospheric pressureagainst the O-ring seal 40 mounted in the flange 41 extending from theside plates 32 and 4, and the top and bottom plates 30 and 36 (notshown). Optionally, additional conventional closure clamp or latchdevices can be used to insure closure of the door before chamberevacuation is initiated.

FIG. 5, FIG. 6, and FIG. 7 are cross-sectional views of gas distributiontubes 54, 58, and 56, respectively, showing angular positions of the gasdistribution outlet ports. The outlet ports are positioned to provideplasma flow to all lower portions of the sterilizing chamber 60 wherearticles to be sterilized are placed. Tube 54 shown in FIG. 5 is placedadjacent back plate 37 and directs plasma gases downward and toward thelower center of the chamber through outlet ports 70 and 72,respectively. Tube 58 shown in FIG. 6 is placed adjacent the door 38 anddirects plasma gases downward and toward the lower center of the chamberthrough outlet ports 74 and 76, respectively. Tube 56 shown in FIG. 7 isplaced in the central portion of the chamber 60 and directs plasma gaseslaterally downward through outlet ports 78 and 80. The outlet portsshown for the distribution tubes are representative and can be changedto any other configuration which achieves optimal plasma distribution tothe sterilizing zone or zones of the chamber. Although only one angulararrangement is shown, each tube can have more than one angular set ofoutlet ports, each having different angles, along the length of thetube, as desired. The choice of outlet port angles and locations shouldbe selected in view of how the articles to be sterilized are to beplaced in the chamber and the type of article to be sterilized.

The plasma is preferably directed through a change of direction beforedischarging it into the sterilizing chamber. The flow of plasma thusimpinges on internal surfaces of the gas distribution and sterilizingchamber, thereby cooling it and evenly distributing it. This alsoprevents direct impingement of hot plasma onto the articles beingsterilized, which greatly reduces the oxidation of sensitive packagingmaterials by the activated oxygen atoms in the plasma.

FIG. 8 is a partial top cross-sectional detail fragmentary view ofplasma generator tube 12 of FIG. 3, and FIG. 9 is a more detailed viewof the plasma generator tube outlet assembly shown in FIG. 3. The gasfed to the inlet port 48 flows in the passageway 86. The gas mixturepasses into-the proximal end of the tube 52 and through the excitationzone 87 within the waveguide 8 where the plasma is formed. The proximalend of the plasma generator tube 52 is supported on cylindricalprojection 88. O-ring 90 or another type of seal forms a gas-tight sealtherewith, thereby maintaining a reduced pressure in the tube 52 andpreventing leakage of atmospheric gas into the system.

In this sectional view, an optional plasma starter ionizer is shown. Thetip 81 is connected by an insulated conduit 83 (shown schematically) toa power supply 85 which can be powered with a standard 115 V AC powersource. A ground conduit 89 from the power supply connects to the gasinlet cap 44. The electric field ionizes a portion of the gas moleculesflowing from opening 48 through passageway 86, the ionized gases quicklysupporting a plasma as the gases pass through the zone 87. The ionizercan be placed in any of the inlet gas passageways of any of theembodiments of this invention.

Referring to FIG. 9, the outer surface 92 of the distal end of theplasma generator tube 52 is tapered inward and is sealed by O-ring 94 orother form of seal with the backplate 37. The distal end of tube 52 hasincreased thickness and forms a smooth surfaced venturi restriction 96of reduced cross-sectional area. Cap 98 positioned on the proximal endof plasma distribution tube 56 has a preselected restrictive opening 99of further reduced cross-sectional area. These restrictions are criticalaspects of the preferred embodiment of this invention, creating apressure difference between the low pressure plasma generating zone 87and the vacuum pressure in the distribution tube 56 and sterilizingchamber 60.

The diameter of the restriction diameter 99 is selected to maintain adesired back pressure. This pressure provides optimum energy consumptionand plasma generation with the gas mixture and is a major factor for theproduction of a high yield of plasma at a minimum temperature and withthe minimum power requirement achieved with the device of thisinvention. We prefer to maintain the gas pressure in the plasmagenerating chamber at 0.01 to 50 Torr, preferably at 0.1 to 15 Torr. Formost operating parameters, the restriction 99 can have a diameter offrom about 4.82 to about 8.00 mm and preferably from about 6.28 to about6.54 mm.

FIG. 10 is a cross-sectional view of the waveguide of the embodiment ofFIG. 1, taken along the line 10--10 in FIG. 3. The waveguide is formedof top and bottom plates 100 and 102, side plates 104 and 106 (FIG. 3),and end plates 108 and 110, welded or bolted together. A singlemagnetron rod 112 is placed in the end of the waveguide 8. The plasmagenerating tubes 51, 52, and 53 are positioned in the waveguide 8. Thepositions of the plasma generating tubes are selected to provide maximumconversion of the electromagnetic field energy to plasma. Tube 53 ispositioned in a zone to interact with a third of the field and not withzones of the field which will interact with tubes 51 and 52. Tube 52 ispositioned in a zone to interact with a third of the field (half of theremaining field) and not with the field zone which will interact withtube 51. Tube 51 is positioned to interact maximally with the remainderof the field. With this configuration, a single magnetron can be used togenerate plasma with a plurality of gas generating tubes. The preciseplacement of the tubes which will accomplish this result will dependupon the dimensions of the wave guide and the wavelength or frequency ofthe energizing wave.

Three tubes have been shown in FIG. 10 by way of example and not by wayof limitation. Any number, odd or even, of tubes can be used up untilthe total power of the electromagnetic field is absorbed.

FIG. 11 is a front cross-sectional view of an alternate single waveguide embodiment of the plasma sterilizer of this invention. Threeplasma generating units 120 are positioned above the sterilizing chamber122 defined by upper plate 124, lower plate 126, back plate 128, backplate 130, and side plates 128 and 132. The door plate (not shown) canbe mounted to the front of the chamber as described above with respectto FIG. 2 and FIG. 3 and forms a sealed engagement with the front edgesof the chamber walls. The gases are exhausted from the chamber throughexhaust ports 136 in the floor plate 126.

The plasma generators comprise an inlet port for the gas mixture leadingto the plasma generating tubes 139, 140, and 141 positioned in thewaveguide 142 where the gases are energized and converted to a plasma.The plasma is directed by the plasma distributors 144 to the interior ofthe sterilizing chamber 122. Each plasma distributor 144 can have aT-configuration described below in detail with respect to the embodimentof FIG. 14. The distributor can have any shape and size whichdistributes the plasma gases uniformly throughout the sterilizingchamber. The plasma generating source in this embodiment is a magnetron146 positioned at the end of the waveguide 142.

FIG. 12 is a cross-sectional view of the waveguide of embodiment of FIG.11, taken along line 12--12 in FIG. 11. The waveguide is formed of topand bottom plates 150 and 152 (FIG. 11), side plates 154 and 156, andend plates 158 and 160, welded or bolted together. A single magnetronrod 162 is placed in the end of the waveguide 142. The plasma generatingtubes 139, 140, and 141 are positioned in the waveguide 142. Thepositions of the plasma generating tubes are selected to provide maximumconversion of the electromagnetic field energy to plasma. Tube 141 ispositioned in a zone to interact with a third of the field and not withzones of the field which will interact with tubes 140 and 139. Tube 140is positioned in a zone to interact with a third of the field (half ofthe remaining field) and not with the field zone which will interactwith tube 139. Tube 139 is positioned to interact maximally with theremainder of the field. With this configuration, a single magnetron canbe used to generate plasma with a plurality of gas generating tubes.

The precise placement of the tubes which will accomplish this resultwill depend upon the dimensions of the wave guide and the wavelength orfrequency of the energizing wave. Three tubes have been shown in FIG. 12by way of example and not by way of limitation. Any number, odd or even,of tubes can be used up until the total power of the electromagneticfield is absorbed.

The detailed construction of the plasma generator tube and plasmadistribution tube seals and flow restrictors have the same configurationas the corresponding elements in the embodiment of FIG. 11 and aredescribed in greater detail hereinabove in conjunction therewith.

FIG. 13 is a front cross-sectional view of a multiple magnetronembodiment of this invention, and FIG. 14 is a side cross-sectional viewtaken along the line 14--14 in FIG. 13. Three plasma generators 208 ofthis embodiment are positioned above the sterilizing chamber cavity 229,each producing a plasma generated from the gas mixture introducedthrough inlets 210 to a plasma generating tube 230 positioned in therespective waveguides 202. The plasma produced is fed by plasmagenerating tubes 230 through respective gas distributors 211, 212, and213 into the sterilizing chamber 229. The distributor tubes can have anylength and configuration required for distributing the plasma gasesuniformly throughout the sterilizing chamber. Distribution tubes made ofnon-fragile materials are particularly advantageous. Suitablenon-fragile tubes can be made of oxidation resistant metals such asstainless steel. Optimally, they are made of a plasma resistant polymersuch as a fluorocarbon polymer, e.g., TEFLON.

The sterilizing chamber 229 is constructed from metal plates welded toform a gas-tight construction which is able to withstand externalpressures when the chamber is evacuated. The construction comprises topplate 214, bottom plate 216, back plate 218, side plates 217 and 219.Exhaust ports 222 are mounted in the bottom plate 216. The door 224 issupported by conventional pin hinges or the like (not shown) mounted onthe side, top, or bottom of the chamber walls as described above withrespect to the embodiment of FIG. 1. The door 224 is held in sealingengagement by atmospheric pressure against the O-ring seal 225 mountedin the flange 227 extending from the side plates 217 and 219, and thetop and bottom plates 214 and 216 (not shown). Optionally, additionalconventional closure clamp or latch devices can be used to insureclosure of the door before chamber evacuation is initiated.

Referring to FIG. 14, the gas mixture is fed to the inlet port 210 byconduit 235 and then to the plasma generating tube 230 where it isenergized to form a gas plasma. The control valves and CPU can be any ofthe conventional, standard devices used for gas flow control in plasmagenerating equipment. The waveguide 202 guides the electromagnetic wavesgenerated by the magnetron 206 in a pattern which concentrates theelectromagnetic energy in a zone in which the plasma generator tube 230is positioned. A tuning rod 240 can be vertically positioned to tune theelectromagnetic waves to provide optimum plasma generation. The gasplasma is then fed to the gas distributor 212 and its Y-orT-distribution section 241. The horizontal distributors have angularoutlet ports positioned and with angular displacement as described withrespect to the preferred embodiment of FIG. 5, FIG. 6, and FIG. 7. Theplasma is directed through a change of direction, for example, 90°,twice before it is discharged into the sterilizing chamber. Thisprevents direct impingement of hot nascent plasma onto the articlesbeing sterilized, greatly reducing the oxidation of sensitive packagingmaterials by the activated oxygen atoms in the plasma.

FIG. 15 is a fragmentary, cross-sectional view of the plasma generatingtube of the plasma generator shown in FIG. 14, showing details of thetube construction and its connection with the gas distributor tube. Thetube 230 is held in a sealed engagement with the heat radiating cap 250by O-ring 252 or a similar seal. The lower distal end of the tube isalso held in a sealed engagement with the lower heat radiator sleeve 254by an O-ring 256. The proximal end of the distribution tube 212 extendsinto the distal end of tube 230 and is held in a sealed relationshipwith the lower heat radiator sleeve by an O-ring 258. Cap 260 ispositioned on the proximal end of plasma distribution tube 212 and has apreselected restrictive opening 262 of further reduced cross-sectionalarea. As described with respect to the embodiment shown in FIG. 9, therestriction is a critical aspect of the invention, creating a pressuredifference between the low pressure plasma generating zone and thevacuum pressure in the distribution tube and sterilizing chamber.

The diameter of the restriction diameter 262 is selected to maintain thedesired back pressure, as already discussed for restriction 99.

The embodiments of this invention have been presented with three plasmagenerating units. The number of generating units is not critical, beingselected to provide a good plasma distribution in the particularsterilizing chamber used. Any desired number of plasma generators can beused with each sterilizing chamber and are intended to be includedwithin the scope of this invention. It will be also be readily apparentthat any number of gas plasma tubes can be positioned to interact withthe electromagnetic field generated from a single magnetron with thiswaveguide configuration, and that other waveguide configurations can beused to achieve this effect. The preferred plasma generating tubes andplasma distributing tubes are made of quartz. However, any othermaterials with the necessary physical, chemical, and electricalproperties for plasma generation in an electromagnetic field can be usedfor the plasma generating tubes. Similarly, the conduits and tubing usedfor transport of plasma from the plasma generator to the sterilizingchamber can be any solid material which has the requisite shape andstrength and which is resistant to chemical action and degradation bythe plasma gases. Suitable transport conduit materials include quartzand other plasma corrosion resistant glasses, stainless steel andother-oxidation resistant metals, and oxidation resistant plastics suchas fluorocarbon polymers, e.g. TEFLON and the like, and siloxanepolymers.

The apparatus of this invention generates a sterilizing species derivedfrom a mixture of noble gas (e.g. argon or helium), oxygen, andhydrogen, as is exemplified hereinafter. The sterilization is carriedout at a vacuum pressure of from about 0.1 to 150 torr and preferablyfrom 1 to 40 torr. The temperature in the sterilizing chamber ismaintained below 63° C., and preferably is from about 38° C. to about54° C. Under these conditions, effective sterilization is effectedwithout significant deterioration of packaging materials in whicharticles to be sterilized may be placed.

The method of this invention for plasma sterilization comprises exposingan article to be sterilized to a plasma generated from a gaseous mixtureof argon mixed with oxygen and hydrogen at temperatures of less than 63°C., a pressure of from 0.1 to 150 torr, and a treatment time of at least5 minutes, and preferably from 10 to 15 minutes. For sterilizingpackaged goods, the gas mixture from which the plasma is generated mostpreferably contains about 2.8 (v/v) percent oxygen and 2.2 (v/y) percenthydrogen, the balance being a noble gas.

Packages for sterilization are treated for at least 15 minutes andpreferably from 1 to 5 hours. In an alternate embodiment, packaged goodsare sterilized by treatment for at least 15 minutes and preferably from1 to 5 hours with plasma generated from the gas mixture.

A residence time of from 5 to 10 minutes is usually sufficient tosterilize most articles. Clean articles packaged in envelopes or othershapes having porous surfaces allowing easy penetration of the plasmaare usually completely sterilized within 60 minutes.

In an optimum method of sterilizing, the articles to be sterilized areplaced in the sterilizing chamber, supported by conventional grids whichpermit the plasma to reach all surfaces of the articles. The chamber isclosed, the sterilizing chamber is evacuated, plasma generation isbegun, and the plasma is directed into and through the sterilizingchamber.

The plasma components have a short life, and quickly decay to formnon-toxic components usually found in air. These are fully acceptable asresidues or as exhaust gas components.

A particularly preferred gas mixture embodiment of the invention wasprepared with oxygen, hydrogen, and the balance argon, which was used inpracticing the method and apparatus of the invention and shown to havesuitable sporicidal activity, as exemplified by the following Example 1and with reference to FIG. 16.

EXAMPLE 1

Biological indicators are characterized preparations of specificmicroorganisms resistant to a particular sterilization process. They areused to assist in the qualification of the physical operation ofsterilization apparatus and to validate a sterilization process for aparticular article. They typically incorporate a viable culture of aknown species of microorganism, usually spores. Under the rightconditions, sterilization can approximate first order kinetics, and thusallow sterilization cycle times to be readily determined. Biologicalindicators were prepared as follows and used to exemplify the presentinvention.

Packages for the biological indicators were obtained from BaxterLaboratories as "Plastipeel Pouches." These pouches have an upper sheetof a gas permeable fabric of bound polyethylene fibers ("Tyvek"), whichis already sealed on three edges and where the user seals the fourthedge, after insertion of the carrier, to a lower sheet of impermeableclear polyester film ("Mylar"). Filter paper disks (1/4 inch diameterSchleicher & Schuell 740E) were used as carriers for spores. Each diskwas inoculated with 5 to 6 logs of spores of a viable organism, whichwas chosen to be B. circulans. B. circulans is advantageous as theorganism as it has been found to have a higher resistance and morestable resistant pattern when compared to prior art organisms such as B.subtilis and B. stearothermophilus, as described in Ser. No. 08/111,989,filed Aug. 25, 1993, of common assignment herewith.

Exposure intervals for exposure to the sterilizing gas mixture werechosen, and the biological indicators were placed into the sterilizerapparatus. The biological indicators were exposed to a plasma cycle forthe selected exposure required time intervals. The plasma generatedgaseous mixture was oxygen 2.8 (v/v) percent and hydrogen 2.2 (v/v)percent and the rest argon. A plasma cycle was flowing the gas mixtureembodiment at a volume of about 2.2 standard 1/min.

After exposing the biological indicators to the sterilizing gastreatment at different times (the wall temperature was maintained atabout 95° F.), the indicators were removed and tested for sterility.

Each pouch was cut open and each carrier was aseptically transferred tolabelled, individual grind tubes. Each tube was vortexed until thecarriers were macerated. Each macerated carrier was serially dilutedusing standard plate count techniques. The number of surviving spores(if any) were determined under spore growth conditions.

Survivor curves were generated with the number of surviving spores beingdetermined as a function of exposing step time. D-values for theseparate components were calculated using linear regression analysis.D-values (decimal reduction) are the time required at a given set ofexposure conditions to reduce a specific population by 90%, and are thenegative reciprocal of the slope of the line fitted to the graph of thelogarithm of the number of survivors versus time.

Following the experimental methodology just described, survival datawere determined, as described below.

Three pouches per run were exposed to the plasma phase for one of thefollowing time intervals: 4, 8, 12, 16, 20, or 60 minutes. Threeunexposed carriers were used as positive controls. The results forexposures up to 20 minutes are graphically illustrated by FIG. 16, anddemonstrate that the "D value" calculated from the straight line portionof the curve was 2.8 minutes with tailing observed after a 4.5 logreduction in population. Plasma phase exposure after 60 minutes did notresult in significant additional lethality. These results demonstratethat for the vast majority of infection control applications with knownquantity and resistance of pre-processing bioburden contamination, thisprocess will provide sterile articles without compromising theenvironment, the sterile barrier properties of the package material usedto enclose the article, or the functional properties of the article asdiscussed above.

It is to be understood that while the invention has been described abovein conjunction with preferred specific embodiments, the description andexamples are intended to illustrate and not limit the scope of theinvention, which is defined by the scope of the appended claims.

It is claimed:
 1. A method for plasma sterilization comprising:generating a plasma in a plasma generating chamber; passing said plasma from said plasma generating chamber via a restriction means and a plasma distribution means to a sterilizing chambers, said restriction means and said plasma distribution means providing an indirect passageway which prevents direct impingement of nascent plasma generated in said plasma generating chamber; and, exposing an article to be sterilized to neutral active species of the plasma in said sterilizing chamber to effect sterilization therein, wherein the neutral active species are generated from a gas mixture of a noble gas and having about 2.0 to 2.4 (v/v) percent hydrogen and about 2.6 to 3.0 (v/v) percent oxygen therein.
 2. The method of claim 1 wherein the article is enclosed in a gas permeable container, and the container is surrounded by sterilizing species from the gas plasma during exposure thereof.
 3. The method for plasma sterilization as in claim 1 wherein:the gas mixture is delivered premixed to the plasma generating chamber from a pressurized gas source.
 4. The method for plasma sterilization as in claim 3 wherein the exposing step includes at least one combination sterilizing cycle, each combination sterilizing cycle including a pulsed exposure to gaseous anti-microbial agents in addition to pulsed exposure to neutral active species of the plasma.
 5. The method for plasma sterilization as in claim 4 Wherein the gaseous anti-microbial agent of the pulsed exposure is removed before introduction of the neutral active species of the plasma. 